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The guided bone regeneration (GBR) technique is the most common and durable approach to repairing bone defects in periodontal surgery. However, membrane exposure causes bacterial infiltration, which lowers the functional integrity of the barrier membrane and destroys bone repair. Here, an antibacterial peptide-modified small intestinal submucosa (SIS) membrane is used as a new GBR membrane for effective bone regeneration. The peptide JH8194 was placed into chitosan microspheres to preserve its stability and allow for sustained release, which realizes rapid and efficient functional modification of the SIS membrane. Biocompatibility and certain antibacterial activities were found in the modified SIS membrane (SIS@CS-JH8194). Additionally, in vitro experiments showed that SIS@CS-JH8194 promoted the expression of osteogenic-related factors and decreased the secretion of inflammatory factors in rat bone mesenchymal stem cells. In vivo experiments showed that SIS@CS-JH8194 could effectively promote bone regeneration in rat skull defects. In this work, we created a new antibacterial GBR membrane to help avoid postoperative infection and improve bone tissue regeneration. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronological aging has long been considered an immutable risk factor for cerebral small vessel disease, but recent studies have revealed the potential for biological aging to be modulated and possibly even slowed or reversed, offering a promising avenue for intervention. Emerging studies have reported that biological aging biomarkers, such as leukocyte telomere length and epigenetic clocks, are associated with the risk of cerebral small vessel disease. However, the results remain inconsistent and controversial. Hence, in this study, we sought to explicate the underlying causal relationship between biomarkers of aging and cerebral small vessel disease. The results show that genetically determined leukocyte telomere length and epigenetic clocks were not associated with the ten measures of cerebral small vessel disease. Our study did not provide evidence to support a causal association between cerebral small vessel disease and the aging biomarkers of leukocyte telomere length and epigenetic clocks; thus, more studies are needed to evaluate the potential of reverse-biological-aging therapy in cerebral small vessel disease. Biological aging biomarkers, such as leukocyte telomere length (LTL) and epigenetic clocks, have been associated with the risk of cerebral small vessel disease (CSVD) in several observational studies. However, it is unclear whether LTL or epigenetic clocks play causal roles as prognostic biomarkers in the development of CSVD. We performed a Mendelian randomization (MR) study of LTL and four epigenetic clocks on ten subclinical and clinical CSVD measures. We obtained genome-wide association (GWAS) data for LTL from the UK Biobank (N = 472,174). Data on epigenetic clocks were derived from a meta-analysis (N = 34,710), and CSVD data (N cases =1293–18,381; N controls = 25,806–105,974) were extracted from the Cerebrovascular Disease Knowledge Portal. We found that genetically determined LTL and epigenetic clocks were not individually associated with ten measures of CSVD (IVW p > 0.05), and this result was consistent across sensitivity analyses. Our findings imply that LTL and epigenetic clocks may not help in predicting CSVD development as causal prognostic biomarkers. Further studies are needed to illustrate the potential of reverse biological aging in serving as an effective form of preventive therapy for CSVD. [ABSTRACT FROM AUTHOR]

Guided bone regeneration (GBR) is a promising strategy for repairing bone defects using bioactive membranes. In this study, a new type of GBR membrane based on the small intestinal submucosa (SIS) was created, and its surface structure, cytological characteristics, and bone defect repair ability were compared with commonly used membranes. Our results show that compared to the Heal-all and Dentium membranes, the SIS membrane has an asymmetric structure that does not affect the proliferation of bone marrow mesenchymal stem cells (BMSCs). Instead, it increased their formation of calcium nodules and expression of bone morphogenetic protein-2 (BMP-2), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and osteopontin (OPN). Six weeks after their insertion into a rat calvarial defect model, increased bone growth was observed in the SIS membrane group. Our results indicate that the SIS membrane has good biocompatibility and is more effective in promoting early bone formation than existing membranes. Given the wide range of source materials and simple preparation processes available, SIS membrane is a promising candidate for guided bone regeneration. [ABSTRACT FROM AUTHOR]

This letter to the editor discusses the successful treatment of a 16-year-old boy with concurrent vitiligo and atopic dermatitis using the JAK inhibitor upadacitinib. The article explains that vitiligo is a depigmentation disorder caused by the destruction of melanocytes, and atopic dermatitis is characterized by a type 2 immune response. The authors suggest that there may be a potential association between vitiligo and atopic dermatitis due to overlapping genetic and immune mechanisms. The patient in the case study experienced repigmentation and relief from symptoms after treatment with upadacitinib. The authors conclude that upadacitinib can be an effective treatment option for patients with both vitiligo and atopic dermatitis. [Extracted from the article]

Guided bone regeneration (GBR) technology is the most widely used and stable method for bone defect repair. However, infectious bone defect limits the application of this technique. Herein, a small intestinal submucosa (SIS) membrane modified by chimeric peptides as a new type of GBR membrane is developed for efficacious tissue regeneration. Based on the main components of SIS membrane are I and III collagen, collagen binding peptides TKKTLRT and KELNLVY sequences are used to construct chimeric peptides with healing‐promoting peptide Hst1 or antibacterial osteogenic peptide JH8194, so as to realize the specifically target of SIS. This method achieves the fast and efficient multifunctional modification of SIS membrane. The chimeric peptides modified SIS (pSIS) membrane has satisfactory biocompatibility and a certain degree of antibacterial activity. Moreover, pSIS promotes the osteogenic related factors expression of rat bone mesenchymal stem cells and demonstrates great bone regeneration in rat skull defect model. Furthermore, pSIS accelerates the migration of oral epithelial cells in vitro and activate integrin α3β1 signal pathway contribute to wound healing. This study presents a novel biomaterial design of GBR membrane, specifically for the treatment of infectious bone defects. [ABSTRACT FROM AUTHOR]

Background: In the spectrum of Alzheimer's Disease (AD) and related disorders, the resting-state functional magnetic resonance imaging (rs-fMRI) signals within the cerebral cortex may exhibit distinct characteristics across various frequency ranges. Nevertheless, this hypothesis has not yet been substantiated within the broader context of whole-brain functional connectivity. This study aims to explore potential modifications in degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) among individuals with amnestic mild cognitive impairment (aMCI) and AD, while assessing whether these alterations differ across distinct frequency bands., Methods: This investigation encompassed a total of 53 AD patients, 40 aMCI patients, and 40 healthy controls (HCs). DC and VMHC values were computed within three distinct frequency bands: classical (0.01-0.08 Hz), slow-4 (0.027-0.073 Hz), and slow-5 (0.01-0.027 Hz) for the three respective groups. To discern differences among these groups, ANOVA and subsequent post hoc two-sample t-tests were employed. Cognitive function assessment utilized the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA). Pearson correlation analysis was applied to investigate the associations between MMSE and MoCA scores with DC and VMHC., Results: Significant variations in degree centrality (DC) were observed among different groups across diverse frequency bands. The most notable differences were identified in the bilateral caudate nucleus (CN), bilateral medial superior frontal gyrus (mSFG), bilateral Lobule VIII of the cerebellar hemisphere (Lobule VIII), left precuneus (PCu), right Lobule VI of the cerebellar hemisphere (Lobule VI), and right Lobule IV and V of the cerebellar hemisphere (Lobule IV, V). Likewise, disparities in voxel-mirrored homotopic connectivity (VMHC) among groups were predominantly localized to the posterior cingulate gyrus (PCG) and Crus II of the cerebellar hemisphere (Crus II). Across the three frequency bands, the brain regions exhibiting significant differences in various parameters were most abundant in the slow-5 frequency band., Conclusion: This study enhances our understanding of the pathological and physiological mechanisms associated with AD continuum. Moreover, it underscores the importance of researchers considering various frequency bands in their investigations of brain function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hu, Wang, Abdul, Tang, Feng, Mu, Ge, Liao and Ding.)

The guided bone regeneration (GBR) technique is the most common and durable approach to repairing bone defects in periodontal surgery. However, membrane exposure causes bacterial infiltration, which lowers the functional integrity of the barrier membrane and destroys bone repair. Here, an antibacterial peptide-modified small intestinal submucosa (SIS) membrane is used as a new GBR membrane for effective bone regeneration. The peptide JH8194 was placed into chitosan microspheres to preserve its stability and allow for sustained release, which realizes rapid and efficient functional modification of the SIS membrane. Biocompatibility and certain antibacterial activities were found in the modified SIS membrane (SIS@CS-JH8194). Additionally, in vitro experiments showed that SIS@CS-JH8194 promoted the expression of osteogenic-related factors and decreased the secretion of inflammatory factors in rat bone mesenchymal stem cells. In vivo experiments showed that SIS@CS-JH8194 could effectively promote bone regeneration in rat skull defects. In this work, we created a new antibacterial GBR membrane to help avoid postoperative infection and improve bone tissue regeneration.

A slow vascularization rate is considered one of the major disadvantages of biomaterials used for accelerating wound healing. Several efforts, including cellular and acellular technologies, have been made to facilitate biomaterial-induced angiogenesis. However, no well-established techniques for promoting angiogenesis have been reported. In this study, a small intestinal submucosa (SIS) membrane modified by an angiogenesis-promoting oligopeptide (QSHGPS) screened from intrinsically disordered regions (IDRs) of MHC class II was used to promote angiogenesis and accelerate wound healing. Because the main component of SIS membranes is collagen, the collagen-binding peptide sequence TKKTLRT and the pro-angiogenic oligopeptide sequence QSHGPS were used to construct chimeric peptides to obtain specific oligopeptide-loaded SIS membranes. The resulting chimeric peptide-modified SIS membranes (SIS-L-CP) significantly promoted the expression of angiogenesis-related factors in umbilical vein endothelial cells. Furthermore, SIS-L-CP exhibited excellent angiogenic and wound-healing abilities in a mouse hindlimb ischaemia model and a rat dorsal skin defect model. The high biocompatibility and angiogenic capacity of the SIS-L-CP membrane make it promising in angiogenesis- and wound healing-related regenerative medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Injectable thermo-sensitive hydrogels composed of small intestinal submucosa (SIS) with exosomes derived from bone marrow mesenchymal stem cells (BMSCs) are desired for bone regeneration. However, poor mechanical properties limit the clinical application of SIS hydrogels. Herein, the mechanical properties of SIS hydrogels incorporated with 3-(3,4-dihydroxyphenyl) propionic acid (CA) are assessed. The results show that the mechanical properties of SIS hydrogels are improved. In addition, the retention and stability of exosomes over time at the defect site are also challenges. Fusion peptides are designed by connecting collagen-binding domines (CBDs) of collagen type I/III with exosomal capture peptides CP05 (CRHSQMTVTSRL) directly or via rigid linkers (EAAAK). In vitro experiments demonstrate that fusion peptides are contribute to promoting the positive effect of exosomes on osteogenic differentiation of BMSCs. Meanwhile, the results of hydrogels combining exosomes and fusion peptides in the treatment of rat skull defect models reveal that fusion peptides could enhance the retention and stability of exosomes, thereby strengthen the therapeutic effect for skull defects. Therefore, SIS hydrogels with CA modified by fusion peptides and exosomes appear to be a promising strategy in bone regenerative medicine., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Ltd.)

Background: The prevalence of Alzheimer's disease (AD) comorbid with depression is common. However, the mechanisms of AD with depression remain unclear., Aims: To investigate the regional alterations of brain activity of AD with depression in resting-state functional magnetic resonance imaging (rs-fMRI)., Methods: 154 patients with AD who met the inclusion criteria were recruited from the Zhejiang Provincial People's Hospital from October 2014 to October 2016. According to whether the core symptoms of depression were present, patients were divided into two groups, 22 patients with AD with depression (AD-D) and 52 patients with AD without depression (AD-nD). The amplitude of low frequency fluctuations (ALFF) was compared between two groups by performing independent-samples t -test., Results: Compared with the AD-D group, increased ALFF values in the bilateral superior frontal gyrus, left middle frontal gyrus and left inferior frontal gyrus were observed in the AD-nD group. The brain activity in the AD-nD group in the bilateral superior frontal gyrus, left middle frontal gyrus and the left inferior frontal gyrus was higher than the AD-D group., Conclusions: Resting-state brain functional alterations may be closely bound up with the pathophysiologic features of patients with AD with depressive symptoms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)